© megaflopp/stock.adobe.com
The EU-funded APTADEGRAD project has developed a new therapy that could help heal diabetic wounds – more specifically, diabetic foot ulcers, one of the disease’s major complications. These chronic wounds affect about a quarter of the more than 800 million people with diabetes worldwide. They can lead to hospitalisation, limb amputation and even death if not treated properly. The APTADEGRAD therapy has the potential to transform the landscape of wound care, offering a genuine cure rather than mere management for millions of patients.
A crisis of chronic inflammation
Mortality statistics for diabetes are stark: around 5 % of patients die within a year of developing diabetic foot ulcers, a figure that rises to 42 % after five years. Even so, current treatments involve simply cleaning and dressing the ulcers. “You are treating the symptoms, but you don’t have an approved drug for a disease-modifying approach,” explains Juan Ruiz-Constantino, CEO of Lincbiotech, the Spanish biotechnology company coordinating the project, in a recent news item(opens in new window). APTADEGRAD’s solution, on the other hand, tackles the root of the problem: the inflammation that makes these chronic wounds so hard to heal.
While inflammation normally helps fight infection and aids tissue repair, in diabetic wounds, proteins such as IL-1β, its receptor IL-1R1 and MMP-9 accumulate to toxic levels, preventing the healing process from progressing. Existing antibody therapies can block these proteins but cannot remove them from the wound environment, limiting their effectiveness.
To address this, APTADEGRAD researchers have pioneered a novel class of compounds known as lysosome-targeting chimeras (LYTACs). Unlike antibodies that merely block proteins, LYTACs act as miniature delivery systems that actively remove them. One end of the molecule captures the excess inflammatory protein, while the other binds to receptors on the cell surface. This triggers the cell to internalise the whole complex and deliver it to the lysosome – the cell’s natural recycling centre – where both the drug and the protein are broken down.
“The lysosomes are part of the quality control system we have inside our cells,” states Ruiz-Constantino. By recruiting this internal waste disposal system, the therapy reduces protein levels in a controlled manner, maintaining enough proteins to support healing and restoring a balanced inflammatory response without eliminating the proteins entirely.
Early results from the project, which runs until 2027, have been very encouraging. In diabetic wound models, the LYTAC-based compounds accelerated healing and dampened inflammation, often performing as well as or better than traditional antibody treatments.
For its trials, the APTADEGRAD (A novel, first-in-its-kind, aptamer-based LYTACs to address the unmet clinical need of diabetic wounds.) team has developed both injections administered under the skin near ulcers and a hydrogel capable of gradual release directly onto the wound. While the immediate focus is diabetic foot ulcers, the technology also holds promise for treating other chronic wounds and inflammatory diseases. The next major milestone is generating sufficient safety and efficacy data to support human clinical trials, which researchers hope to commence around 2030.
For more information, please see:
APTADEGRAD project